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Several models have been developed to analyse cortical activity in response to salient events constituted by multiple sensory modalities. In particular, additive models compare event‐related potentials (ERPs) in response to stimuli from two or more concomitant sensory modalities with the ERPs evoked by unimodal stimuli, in order to study sensory interactions. In this approach, components that are not specific to a sensory modality are commonly disregarded, although they likely carry information about stimulus expectation and evaluation, attentional orientation and other cognitive processes. In this study, we present an analytical method to assess the contribution of modality‐specific and nonspecific components to the ERP. We developed an experimental setup that recorded ERPs in response to four stimulus types (visual, auditory, and two somatosensory modalities to test for stimulus specificity) in three different conditions (unimodal, bimodal and trimodal stimulation) and recorded the saliency of these stimuli relative to the sensory background. Stimuli were delivered in pairs, in order to study the effects of habituation. To this end, spatiotemporal features (peak amplitudes and latencies at different scalp locations) were analysed using linear mixed models. Results showed that saliency relative to the sensory background increased with the number of concomitant stimuli. We also observed that the spatiotemporal features of modality‐specific components derived from this method likely reflect the amount and type of sensory input. Furthermore, the nonspecific component reflected habituation occurring for the second stimulus in the pair. In conclusion, this method provides an alternative to study neural mechanisms of responses to multisensory stimulation. [ABSTRACT FROM AUTHOR]

Objective: South Africa has a high burden of HIV infection and anaemia. These conditions may cause HbA1c to over‐ or underestimate glycaemia; however, this has not been comprehensively investigated in African populations. We assessed the association of anaemia, HIV infection and antiretroviral therapy (ART) with HbA1c, and implications for the detection and diagnosis of diabetes, in a black South African population. Research design and methods: In this population‐based cross‐sectional study in eThekwini municipality (Durban), South Africa, we assessed HbA1c and conducted oral glucose tolerance tests (OGTTs), HIV diagnostic tests and full blood count measurements among 1067 participants without a history of diabetes diagnosis. Linear regression was used to examine differences in HbA1c by anaemia (comparator: no anaemia), or HIV and ART (comparator: no HIV) status. HbA1c‐based diabetes prevalence was compared with OGTT‐based prevalence among individuals with anaemia and with untreated and ART‐treated HIV. Results: In adjusted analyses, normocytic and microcytic anaemia were associated with higher HbA1c compared with no anaemia, whereas macrocytic anaemia and ART‐treated HIV were associated with lower HbA1c compared with no anaemia and no HIV, respectively. However, magnitudes of association were small (range: β = −3.4 mmol/mol or −0.31%, p < 0.001 [macrocytic anaemia] to β= 2.1 mmol/mol or 0.19%, p < 0.001 [microcytic anaemia]). There was no significant difference in diabetes prevalence based on HbA1c or OGTT among individuals with anaemia (2.9% vs. 3.3%, p = 0.69), untreated HIV (1.6% vs. 1.6% p = 1.00) or ART‐treated HIV (2.9% vs. 1.2%, p = 0.08). Conclusions: Our results suggest that anaemia and HIV status appear unlikely to materially affect the utility of HbA1c for diabetes detection and diagnosis in this population. Further studies are needed to examine these associations in sub‐Saharan African populations. [ABSTRACT FROM AUTHOR]

Background. Despite emerging evidence regarding the reversibility of stunting at older ages, most stunting research continues to focus on children below 5 years of age. We aimed to assess stunting prevalence and examine the sociodemographic distribution of stunting risk among older children and adolescents in a Malaysian population. Methods. We used cross-sectional data on 6759 children and adolescents aged 6-19 years living in Segamat, Malaysia. We compared prevalence estimates for stunting defined using the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) references, using Cohen's' coefficient. Associations between sociodemographic indices and stunting risk were examined using mixed-effects Poisson regression with robust standard errors. Results. The classification of children and adolescents as stunted or normal height differed considerably between the two references (CDC v. WHO; κ for agreement: 0.73), but prevalence of stunting was high regardless of reference (crude prevalence: CDC 29.2%; WHO: 19.1%). Stunting risk was approximately 19% higher among underweight v. normal weight children and adolescents (p = 0.030) and 21% lower among overweight children and adolescents (p = 0.001), and decreased strongly with improved household drinking water sources [risk ratio (RR) for water piped into house: 0.35, 95% confidence interval (95% CI) 0.30-0.41, p < 0.001). Protective effects were also observed for improved sanitation facilities (RR for flush toilet: 0.41, 95% CI 0.19-0.88, p = 0.023). Associations were not materially affected in multiple sensitivity analyses. Conclusions. Our findings justify a framework for strategies addressing stunting across childhood, and highlight the need for consensus on a single definition of stunting in older children and adolescents to streamline monitoring efforts. [ABSTRACT FROM AUTHOR]

Background. Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service. Methods. Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test. Results. Our data confirm a high-fidelity service with a failure rate of ∼0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT. Conclusions. NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test. [ABSTRACT FROM AUTHOR]

Background. Recent research implicates antibiotic use as a potential contributor to child obesity risk. In this narrative review, we examine current observational evidence on the relation between antibiotic use in early childhood and subsequent measures of child body mass. Methods. We searched PubMed, Web of Science and the Cochrane Library to identify studies that assessed antibiotic exposure before 3 years of age and subsequent measures of body mass or risk of overweight or obesity in childhood. Results. We identified 13 studies published before October 2017, based on a total of 6 81 332 individuals, which examined the relation between early life antibiotic exposure and measures of child body mass. Most studies did not appropriately account for confounding by indication for antibiotic use. Overall, we found no consistent and conclusive evidence of associations between early life antibiotic use and later child body mass [minimum overall adjusted odds ratio (aOR) reported: 1.01, 95% confidence interval (95% CI) 0.98-1.04, N = 2 60 556; maximum overall aOR reported: 2.56, 95% CI 1.36-4.79, N = 616], with no clinically meaningful increases in weight reported (maximum increase: 1.50 kg at 15 years of age). Notable methodological differences between studies, including variable measures of association and inclusion of confounders, limited more comprehensive interpretations. Conclusions. Evidence to date is insufficient to indicate that antibiotic use is an important risk factor for child obesity, or leads to clinically important differences in weight. Further comparable studies using routine clinical data may help clarify this association. [ABSTRACT FROM AUTHOR]

Abstract: This study explored the effect of different classroom spatial layouts on student perceptions of digital technology in a secondary schooling environment. A quasi‐experimental approach facilitated by a Single Subject research design (SSRD) isolated the impact of two learning spaces—traditional' classrooms, and ‘new generation learning spaces’ (NGLS), on students' perceived effectiveness, use and value of one‐to‐one technology as a learning tool. Results from quantitative analyses over the period of a school year indicated that different spatial configurations had a measurable effect on how students' perceived the effectiveness of the affordances of digital technology, with improvements often linked to NGLS. However, the evidence suggests that a change in learning space alone will not increase learning. A change in space supports those teachers who are able and willing to integrate the affordances of technology into their practice. Building on the collective methodologies of earlier work this analysis has reinforced the credibility of this unique methodological approach, arguing this evaluative strategy offers the capacity to generate much needed robust empirical data on evaluation of learning environments in a secondary school setting. [ABSTRACT FROM AUTHOR]

The in vivo or in vitro formation of Ig G4 hybrid molecules, wherein the immunoglobulins have exchanged half molecules, has previously been reported under experimental conditions. Here we estimate the incidence of polyclonal Ig G4 hybrids in normal human serum and comment on the existence of Ig G4 molecules with different immunoglobulin light chains. Polyclonal Ig G4 was purified from pooled or individual donor human sera and sequentially fractionated using light-chain affinity and size exclusion chromatography. Fractions were analysed by SDS- PAGE, immunoblotting, ELISA, immunodiffusion and matrix-assisted laser-desorption mass spectrometry. Polyclonal Ig G4 purified from normal serum contained Ig G4 κ, Ig G4 λ and Ig G4 κ/ λ molecules. Size exclusion chromatography showed that Ig G4 was principally present in monomeric form (150 000 MW). SDS- PAGE, immunoblotting and ELISA showed the purity of the three Ig G4 samples. Immunodiffusion, light-chain sandwich ELISA and mass spectrometry demonstrated that both κ and λ light chains were present on only the Ig G4 κ/ λ molecules. The amounts of Ig G4 κ/ λ hybrid molecules ranged from 21 to 33% from the five sera analysed. Based on the molecular weight these molecules were formed of two Ig G4 heavy chains plus one κ and one λ light chain. Polyclonal Ig G ( Ig G4-depleted) was similarly fractionated according to light-chain specificity. No evidence of hybrid Ig G κ/ λ antibodies was observed. These results indicate that hybrid Ig G4 κ/ λ antibodies compose a substantial portion of Ig G4 from normal human serum. [ABSTRACT FROM AUTHOR]

Aim The aim of this systematic review was to inform evidence-based clinical practice guidelines for children with cerebral palsy (CP) and low bone mineral density (BMD). Method A computer-assisted literature search was focused on low BMD in children with CP, and was limited to the following interventions: weight-bearing activities, bisphosphonate use, and vitamin D or calcium supplementation. Articles were classified according to American Academy of Neurology guidelines and recommendation classifications were given based on the evidence for the intervention increasing BMD and decreasing fragility fractures. Studies were included if they were English-language full-text studies, focused on children with CP, and included at least 10 participants receiving the studied interventions. Results Twenty-one articles underwent full-text review and data abstraction, including seven studies of weight-bearing activities, five studies of vitamin D or calcium supplementation, and nine studies of bisphosphonates administration. Overall, the evidence that bisphosphonates administration increases BMD was assessed as level B (probable) while the evidence that vitamin D or calcium supplementation does so was assessed as level C (possible); there was insufficient evidence to suggest that weight-bearing activities are an effective intervention to improve BMD. The evidence that bisphosphonates help to prevent fragility fractures was assessed as level C (possible); there was inadequate evidence to support the use of weight-bearing activities or vitamin D or calcium supplementation to decrease fragility fractures. Interpretation Evidence-based clinical practice guidelines were created outlining the suggested role of weight-bearing activities, vitamin D and calcium supplementation, and bisphosphonate use for children with CP with low BMD at risk of fragility fractures. [ABSTRACT FROM AUTHOR]

Child welfare systems have struggled to create innovative, culturally sensitive programmes to address the multiple and pervasive barriers that exist in engaging child welfare parent clients in their service plans. Peer mentor programmes-those in which parents who have successfully navigated the child welfare system and reunified with their children, mentor parents newly entering the system-are designed to address some of these barriers, to improve reunification outcomes. Focus groups with parent clients ( n = 25) and interviews with peer mentors ( n = 6) were conducted to identify the characteristics of peer mentoring programmes that are critically helpful to parent clients, as well as the mechanisms that allow peer mentors to be effective in their work. The qualitative analysis uncovered three general themes to which both parents and peer mentors frequently referred in interviews-the value of shared experiences, communication and support. Additionally, the study found that peer mentorship has positive effects not only on parent clients but also on the mentors themselves. The inclusion of peer mentors in child welfare practice suggests an important paradigm shift within child welfare that could lead to culture change for the field. [ABSTRACT FROM AUTHOR]

The article presents a study on the molecular basis of memory dysfunction in patients with multiple sclerosis (MS). The study compared molecular and morphological changes in demyelinated and myelinated hippocampi from postmortem MS brains to investigate possible mechanisms of memory impairment in patients with MS. Results show that minimal neuronal loss occurred in demyelinated hippocampi but significant decrease in neuronal proteins essential for memory or learning, axonal transport were noted.

Background: One of the principal theories regarding the biological basis of major depressive disorder (MDD) implicates a dysregulation of emotion-processing circuitry. Gender differences in how emotions are processed and relative experience with emotion processing might help to explain some of the disparities in the prevalence of MDD between women and men. This study sought to explore how gender and depression status relate to emotion processing. Methods: This study employed a 2 (MDD status) × 2 (gender) factorial design to explore differences in classifications of posed facial emotional expressions (N=151). Results: For errors, there was an interaction between gender and depression status. Women with MDD made more errors than did nondepressed women and men with MDD, particularly for fearful and sad stimuli (Ps <.02), which they were likely to misinterpret as angry (Ps <.04). There was also an interaction of diagnosis and gender for response cost for negative stimuli, with significantly greater interference from negative faces present in women with MDD compared to nondepressed women (P=.01). Men with MDD, conversely, performed similarly to control men (P=.61). Conclusions: These results provide novel and intriguing evidence that depression in younger adults (<35 years) differentially disrupts emotion processing in women as compared to men. This interaction could be driven by neurobiological and social learning mechanisms, or interactions between them, and may underlie differences in the prevalence of depression in women and men. Depression and Anxiety, 2009. Published 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

This article explores a notion of 'personalising learning' which puts the learner at the centre, supported by mobile technology and teacher mediation. It reports a small study in the Northern Territory of Australia, with indigenous students who were given mobile camera phones to capture aspects of their everyday lives and bring them into school. It found that they created a range of narratives that linked their traditional literacies with 'new literacies'. The article argues that, using tools like these, students can contribute to their curriculum. However, it raises issues of cultural differences between teachers and students, and the importance of developing critical literacy in conjunction with new communication forms and other new literacies. Finally it points to the important role of teachers in leading change in school cultures, and particularly assessment, that will allow these personal contributions to learners' curricula. [ABSTRACT FROM AUTHOR]

HDL is able to displace cell surface-bound hepatic lipase (HL) and stimulate vascular triglyceride (TG) hydrolysis, much like heparin. Displacement appears to be a result of a high-affinity association of HL and apoA-I. HDL varies in its ability to displace HL, and therefore experiments were undertaken to evaluate the impact of HDL composition and structure on HL displacement from cell surface proteoglycans. HDL apolipoprotein and lipid composition directly affect HL displacement. ApoA-II and apoC-I significantly increase HL displacement from the cell surface. While changes in HDL cholesteryl ester and fatty acid content have no effect on HL displacement, increases in HDL phospholipid and TG content significantly inhibit HL displacement. HDL fractions from hyperlipidemic patients are unable to displace HL from the cell surface. These results indicate that the structure and composition of HDL particles in plasma are central to regulation of HL displacement and the hydrolytic activity of HL. [ABSTRACT FROM AUTHOR]

Objective Degeneration of chronically demyelinated axons is a major cause of irreversible neurological decline in the human central nervous system disease, multiple sclerosis (MS). Although the molecular mechanisms responsible for this axonal degeneration remain to be elucidated, dysfunction of axonal Na+/K+ ATPase is thought to be central. To date, however, the distribution of Na+/K+ ATPase has not been studied in MS lesions. Methods The percentage of axons with detectable Na+/K+ ATPase was determined in 3 acute and 36 chronically demyelinated lesions from 13 MS brains. In addition, we investigated whether postmortem magnetic resonance imaging profiles could predict Na+/K+ ATPase immunostaining in a subset (20) of the chronic lesions. Results Na+/K+ ATPase subunits α1, α3, and β1 were detected in the internodal axolemma of myelinated fibers in both control and MS brains. In acutely demyelinated lesions, Na+/K+ ATPase was detectable on demyelinated axolemma. In contrast, 21 of the 36 chronic lesions (58%) contained less than 50% Na+/K+ ATPase-positive demyelinated axons. In addition, magnetic resonance imaging-pathology correlations of 20 chronic lesions identified a linear decrease in the percentage of Na+/K+ ATPase-positive axons and magnetization transfer ratios ( p < 0.0001) and T1 contrast ratios ( p < 0.0006). Interpretation Chronically demyelinated axons that lack Na+/K+ ATPase cannot exchange axoplasmic Na+ for K+ and are incapable of nerve transmission. Loss of axonal Na+/K+ ATPase is likely to be a major contributor to continuous neurological decline in chronic stages of MS, and quantitative magnetization transfer ratios and T1 contrast ratios may provide a noninvasive surrogate marker for monitoring this loss in MS patients. Ann Neurol 2008;63:428-435 [ABSTRACT FROM AUTHOR]

Objective: Degeneration of chronically demyelinated axons is a major cause of irreversible neurological decline in the human central nervous system disease, multiple sclerosis (MS). Although the molecular mechanisms responsible for this axonal degeneration remain to be elucidated, dysfunction of axonal Na+/K+ ATPase is thought to be central. To date, however, the distribution of Na+/K+ ATPase has not been studied in MS lesions.Methods: The percentage of axons with detectable Na+/K+ ATPase was determined in 3 acute and 36 chronically demyelinated lesions from 13 MS brains. In addition, we investigated whether postmortem magnetic resonance imaging profiles could predict Na+/K+ ATPase immunostaining in a subset (20) of the chronic lesions.Results: Na+/K+ ATPase subunits alpha1, alpha3, and beta1 were detected in the internodal axolemma of myelinated fibers in both control and MS brains. In acutely demyelinated lesions, Na+/K+ ATPase was detectable on demyelinated axolemma. In contrast, 21 of the 36 chronic lesions (58%) contained less than 50% Na+/K+ ATPase-positive demyelinated axons. In addition, magnetic resonance imaging-pathology correlations of 20 chronic lesions identified a linear decrease in the percentage of Na+/K+ ATPase-positive axons and magnetization transfer ratios (p < 0.0001) and T1 contrast ratios (p < 0.0006).Interpretation: Chronically demyelinated axons that lack Na+/K+ ATPase cannot exchange axoplasmic Na+ for K+ and are incapable of nerve transmission. Loss of axonal Na+/K+ ATPase is likely to be a major contributor to continuous neurological decline in chronic stages of MS, and quantitative magnetization transfer ratios and T1 contrast ratios may provide a noninvasive surrogate marker for monitoring this loss in MS patients. [ABSTRACT FROM AUTHOR]

Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis may play a role in panic disorder. HPA studies in patients with panic disorder, however, have produced inconsistent results. Seeking to understand the inconsistencies, we reexamined endocrine data from four studies of patients with panic disorder, in light of animal data highlighting the salience of novelty, control, and social support to HPA axis activity. Patients with panic disorder were studied (1) at rest over a full circadian cycle, (2) before and after activation by a panicogenic respiratory stimulant (doxapram) that does not directly stimulate the HPA axis, and (3) before and after a cholecystokinin B (CCK-B) agonist that is panicogenic and does directly stimulate the HPA axis. Patients with panic disorder had elevated overnight cortisol levels, which correlated with sleep disruption. ACTH and cortisol levels were higher in a challenge paradigm (doxapram) than in a resting state study, and paradigm-related ACTH secretion was exaggerated in patients with panic disorder. Panic itself could be elicited without HPA axis activation. Patients with panic disorder showed an exaggerated ACTH response to pentagastrin stimulation, but this response was normalized by prior exposure to the experimental context or psychological preparation to reduce novelty and enhance sense of control. Novelty is one of a number of contextual cues known from animal work to activate the HPA axis. The HPA axis abnormalities seen in patients with panic disorder in the four experiments reviewed here might all be due to exaggerated HPA axis reactivity to novelty cues. Most of the published panic/HPA literature is consistent with the hypothesis that HPA axis dysregulation in panic is due to hypersensitivity to contextual cues. This hypothesis requires experimental testing. Depression and Anxiety 24:66–76, 2007. Published 2006 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In this paper, we explore the rationale, process and outcomes of the Regional Interoperability Project on Progression for Lifelong Learning, a project that established a model of cross-sector collaboration in personal development planning technology in the UK. With specific reference to the widening participation agenda, and grounded in the perspective of lifelong learners, the project tested an approach in which discrete nodes of an individual’s learning journey are joined up through technology services. The paper describes the development of conceptual and practical tools to assist transitions between various communities of learning. A set of scenarios was developed, involving study to study and study to employment, while practical tools included development of UK LeaP draft interoperability standard (BS8788)-compliant links between ePortfolio software, and the actual test transfer of data. The results indicate that recognising the smallest individual elements in the process is important, both in a technical sense and as a means of personalising learning and assisting transition between sectors. Through developing connections between these elements, the project partners engaged in lifelong learning. [ABSTRACT FROM AUTHOR]

Objective In humans, the glucocorticoid corticosterone circulates in blood at 10–20-fold lower levels than cortisol, but is found in higher relative amounts in postmortem brain samples. Access of cortisol and corticosterone to the central nervous system may not be equal. Additionally, the relative affinities for the glucocorticoid and mineralocorticoid receptors differ, such that corticosterone may play a significant role in human brain function. Design We measured cortisol and corticosterone levels in paired plasma and cerebrospinal fluid (CSF) samples. To test the relative potency of cortisol vs. corticosterone on hypothalamic–pituitary–adrenal (HPA) feedback, subjects underwent a three-phase, single-blind, randomized study assessing the postmetyrapone ACTH response over 3 h to an intravenous bolus of vehicle, cortisol or corticosterone (0·15 mg/kg and 0·04 mg/kg). Participants Outpatients undergoing diagnostic lumbar puncture who were subsequently deemed to be free of disease. Feedback was tested in healthy male volunteers. Measurements Plasma and CSF corticosterone to cortisol ratio was calculated and the ACTH response over time after the bolus glucocorticoid measured. Results Plasma corticosterone : cortisol was 0·069 ± 0·007; CSF corticosterone : cortisol was 0·387 ± 0·050 ( P < 0·001). Cortisol and corticosterone (0·15 mg/kg) suppressed ACTH vs. vehicle ( P = 0·002); there was no difference between corticosterone and cortisol. The 0·04 mg/kg dose had no effect on ACTH despite supraphysiological plasma corticosterone levels. Conclusions Corticosterone contributes almost 40% of total active glucocorticoids (cortisol and corticosterone) in the CSF. Significant effects on HPA axis suppression were only seen with supraphysiological levels of corticosterone, suggesting that corticosterone is not important in this model of nonstress-induced ACTH hypersecretion, in which the effect of cortisol predominates. [ABSTRACT FROM AUTHOR]

Major depression is associated to altered hypothalamic-pituitary function. Stress is linked to elevated cortisol as well as menstrual cycle disturbance; however, there is no known relationship between depression and menstrual cycle disruption. The aim of this study was to investigate changes of growth hormone (GH) secretion during the menstrual cycle in normal and depressed women.Case-control study.Nineteen women affected with depression and 24 normal controls were included. The two groups had comparable body mass index (BMI), and age (29·4 ± 9·8vs.28·6 ± 9·7 years). Nine depressed and 10 controls were studied in the follicular phase, while 10 depressed and 14 controls were studied in the luteal phase of the cycle. GH was sampled every 10 min for 24 h, and the data were analysed by the cluster pulse detection method.There was no difference in 24-h mean GH concentrations between depressed and control subjects (P = 0·93), even after accounting for menstrual cycle phase (P = 0·38). GH pulse frequency was higher during the follicular phase of the cycle (P = 0·032), and nocturnal GH was higher in the follicular phase of the cycle (P = 0·05, and after adjusting for 24-h GH,P = 0·0138) regardless of whether the subjects were depressed or healthy.In studies of GH secretion in women with or without depression, it is necessary to control for the phase of menstrual cycle. [ABSTRACT FROM AUTHOR]

Background: Recent evidence suggests that some of the behavioral effects of alcohol may be mediated through actions on nicotinic acetylcholine receptors. Mecamylamine, a nicotinic acetylcholine receptor antagonist, reduces alcohol preference and consumption in alcohol-preferring rats, and in humans, mecamylamine dampens some of the subjective, or mood-altering, effects of alcohol. This experiment was designed to investigate the effects of mecamylamine on consumption of alcohol in healthy social drinkers. Methods: Healthy volunteers (12 men, 12 women) participated in a choice procedure in which they chose between an alcoholic beverage and money (low, medium, or high amounts) after pretreatment with mecamylamine (7.5 or 15 mg) or placebo. Outcome measures were the number of alcoholic beverages consumed and the subjective effects of alcohol. Results: Mecamylamine (15 mg) decreased blood alcohol levels (BALs) after a small fixed dose of alcohol (0.2 g/kg). Even when the lower BALs were taken into account, mecamylamine reduced ratings of stimulation after alcohol (Addiction Research Center Inventory A scale). Mecamylamine did not significantly reduce choice for alcohol versus money. However, there was a tendency for the drug to decrease alcohol choice among participants who reported the greatest stimulant-like effects from alcohol. Conclusion: These results provide only limited support for the idea that nicotinic acetylcholine receptors are involved in the rewarding effects of alcohol. [ABSTRACT FROM AUTHOR]

Puberty is accompanied by a number of changes, among them increased risk for development of major depression. The most common etiology of major depression is stressful life events, being present in approximately 90% of first episodes of depression. The hypothalamic-pituitary-adrenal (IIPA) axis is one of the major systems involved in responses to stress, and this system is clearly influenced by ovarian hormones. Normal women demonstrate resistance to negative feedback of both cortisol in the fast-feedback paradigm and dexamethasone in the standard delayed-feedback paradigm. Depressed premenopausal women show greater increases in baseline cortisol than postmenopausal depressed women and than depressed men. Studies in rodents suggest a similar resistance to glucocorticoid feedback but suggest that estradiol can function to inhibit stress responsiveness. Studies of premenopausal depressed women demonstrate lower estradiol, which suggests that there is less inhibitory feedback of estradiol on the IIPA axis, while normal progesterone continues to augment stress responses further. The onset of these reproductive hormonal changes modulating stress systems at puberty may sensitize girls to stressful life events, which become more frequent at the transition to puberty and young adulthood. [ABSTRACT FROM AUTHOR]

ABSTRACT: The Student Attitudes Toward School Safety Measures (SATSSM) instrument was developed as a new tool to assess high school students' attitudes toward school safety promotion methods. A theory-based pool of statements was scaled using Thurstone's equal appearing interval method by 186 student judges to yield a 30-item instrument. The draft version was operationalized into a 5-point, Likert scale format, using a new sample of 182 students. Exploratory factor analysis suggested three factors: mediation, surveillance, and searching methods. The SATSSM was reduced to six items for each scale with a five-item social desirability scale added, and piloted with 66 new students. Final administration of the SATSSM to 166 new students yielded scale and overall internal consistencies exceeding .80 with low interscale correlations. A simultaneously administered questionnaire measuring perceptions of school safety suggested students possessed increased awareness of school violence, but they believed improving school safety is beyond their school's control. (J Sch Health. 2002;72(3): 107-114) [ABSTRACT FROM AUTHOR]

This study examined the impact of maternal cocaine use and associated risk factors such as polysubstance use, maternal functioning, and caregiving on affect regulation during infancy. Participants were 45 mother-infant dyads (19 cocaine exposed and 26 control infants) recruited at birth. Observations and maternal reports of infant behavior were obtained at 2 and 7 months of age, along with measures of pre- and postnatal substance use, maternal functioning, and caregiving stability. Maternal cocaine use accounted for significant variance in infant positive affect at 2 months. Other substance use and gestational age predicted infant distress to novelty and arousal during developmental assessments. At 7 months, the impact of prenatal cocaine exposure on infant affect regulation was mediated by postnatal alcohol use and caregiving stability. These findings, if replicated, suggest that 1 pathway to later problem behavior reported among substance-exposed children may be through early regulatory problems and the quality of postnatal caregiving. [ABSTRACT FROM AUTHOR]

ABSTRACT: This study examined the influence of demographic characteristics and selected family factors on consumption of a healthy breakfast and lunch and consumption of fruits and vegetables among adolescents. A cross-sectional survey was completed by a representative sample (n=3,155) of students from all high schools in a suburban county near Atlanta, Georgia. Students consuming healthy breakfasts, healthy lunches, and more fruits and vegetables were more likely' to be White or Asian (lunch/fruits and vegetables only), better able to communicate with parents or guardians on serious issues, closely monitored by their parents, living with one or both parents, spending less time at home without adults, perceiving themselves at about the right weight or underweight (lunch/breakfast only), male (lunch/breakfast only), and in 9th or 10th grade (breakfast only). These results suggest family factors should be considered in the development and implementation of nutrition interventions. (J Sch Health. 2001;71(10):483-488) [ABSTRACT FROM AUTHOR]

The article focuses on the preservation of seaweeds to create a natural-looking marine environment. Seaweeds were collected and placed in plastic bags to determine if glycerine could preserve the seaweed with its color. No odors suggestive of deterioration were noted. Recommended procedures are also described by the author.

Based upon epidemiological surveys, adverse childhood events are proposed to be risk factors for adult depressive and anxiety disorders. However, the extent to which these events are seen in clinical patient populations is less clear. We examined the prevalence of a number of proposed risk factors for depression in 650 patients with mood and anxiety disorders at the time of presentation for treatment in an outpatient subspecialty clinic. Emotional abuse, physical abuse, or sexual abuse (childhood adversity) was found in approximately 35% of patients with major depression and panic disorder, was more common in women than men, and was associated with an earlier onset of symptoms. Childhood adversity was also strongly associated with marital discord/divorce, and psychopathology in a parent, suggesting family discord predisposes to childhood abuse. Furthermore, the association of childhood abuse with parental mental illness suggests that genetic and environmental factors are difficult to separate as etiological factors in vulnerability. Depression and Anxiety 5:66–72, 1997. © 1997 Wiley-Liss, Inc [ABSTRACT FROM AUTHOR]

The epidemiology of obesity suggests that, for the majority of individuals, the disorder arises from an interaction between genetic predisposition and lifestyle behaviors such as dietary intake and physical activity. Unravelling the molecular basis of such interactions is complex but is becoming a realistic proposition as evidence emerges from whole genome association studies of genetic variants that are definitively associated with obesity. A range of possible study designs is available for investigating gene-lifestyle interaction, and the strengths and weaknesses of each approach are discussed in this article. Given the likely small main effect of common genetic variants and the difficulties in demonstrating associations of lifestyle factors with future risk of obesity, we would favor an analytical approach based on the clear specification of prior probabilities to reduce the likelihood of false discovery. Mixed approaches combining data from large-scale observational studies with smaller intervention trials may be ideal. In designing new studies to investigate these issues, a key choice is how precisely to quantify the important, but difficult to measure lifestyle behaviors. It is clear from power calculations that an approach based on enhancing precision of measurement of diet and physical activity is critical. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on the National Gallery extension published in an issue in 1983.

The spondylocostal dysostoses (SCDs) are a heterogeneous group of axial skeletal disorders characterized by multiple segmentation defects of the vertebrae (SDV) and abnormality of the thoracic cage with mal-aligned ribs and often a reduction in rib number. The four known monogenic forms of SCD follow autosomal recessive inheritance, have generalized SDV, a broadly symmetrical thoracic cage, and result from mutations in Notch signaling pathway genes-DLL3, MESP2, LFNG, and HES7. Autosomal dominant (AD) SCD has been reported less often, is very variable, and molecular genetic mechanisms remain elusive. Here, we report a three-generation, non-consanguineous family with four affected individuals demonstrating multiple or generalized SDV. Scoliosis was present and the trunk shortened but the ribs were relatively mildly affected. There were no other significant organ abnormalities, no obvious dysmorphic features, neurodevelopment was normal, and all investigations, including mutation analysis of DLL3, MESP2, LFNG, and HES7, were normal. A non-pathogenic variant was detected in LFNG but it did not segregate with the phenotype. This Macedonian kindred adds to knowledge of AD SCD and to our knowledge is the first to be tested for the four Notch pathway genes known to be associated with SCD., ((c) 2010 Wiley-Liss, Inc.)

Background: The growth- and plasticity-associated protein GAP-43 plays a significant role in the establishment and remodeling of neuronal connections. We have previously shown that GAP-43 levels, protein kinase C (PKC) activity, and GAP-43 phosphorylation increase during contextual fear conditioning and that fetal alcohol exposure (FAE) decreases PKC activity and GAP-43 phosphorylation in the hippocampus of adult offspring. Drawing on these observations, we hypothesized that FAE manifests its cognitive impairment by disrupting PKC activation and membrane translocation, thereby decreasing GAP-43 phosphorylation and function., Methods: Three groups of pregnant rat dams (FAE and two control diet groups) were placed on different diet regimens. Offspring from each of these groups were placed into each of four test groups, a contextual fear conditioned (CFC) group, a naïve unhandled group, and two nonlearning stress control groups. Hippocampi were dissected, homogenized, and used to prepare a cytosolic and a membrane fraction. These fractions were probed for total GAP-43, PKC-phosphorylated GAP-43, and several PKC subtypes. PKC activity also was measured in total homogenates., Results: Compared with both control diet groups, FAE animals showed a deficit in the activation of PKC in the hippocampus at 24 hr but not at 1.5 hr after CFC. Likewise, we found that the amount of GAP-43 and its phosphorylation were decreased 24 hr after CFC in FAE rats but not at early times after training. Analysis of the translocation of various PKC isoforms revealed that FAE animals had decreased levels of membrane-bound PKC beta2 and PKC epsilon 24 hr after CFC., Conclusions: Considering the role of PKC activation and GAP-43 phosphorylation in synaptic plasticity, our results suggest that deficient translocation of PKC beta2 and PKC epsilon in the hippocampus may mediate the electrophysiological and behavioral deficits observed in fetal alcohol exposed animals.

Background: There has been renewed interest in interactions between stress and use of drugs and alcohol. Although there is evidence that stress increases drug use in human drug users and in laboratory animals, the processes by which stress affects drug-motivated behavior are not understood. Here we examined the effects of an acute social stressor (performing a mental arithmetic task in front of an audience) on consumption of ethanol or placebo beverages in healthy social drinkers., Methods: Thirty-seven men and women, ages 21-35, were randomly assigned to a placebo (n = 15) or ethanol group (n = 22). Subjects participated in two sessions, one with stress (Trier Social Stress Test) the other without stress. In each session, immediately after the stress or no-stress period, subjects consumed the first dose (placebo or 0.3 g/kg of ethanol for men or 0.2 g/kg for women). Then, subjects were allowed to choose up to six more beverages (0.1 g/kg each for the ethanol group or placebo beverages for the placebo group). Measures included percentage of beverage consumed, salivary cortisol level, heart rate, blood pressure, and subjective ratings of mood and drug effect., Results: Subjects in both the placebo and ethanol groups consumed significantly more of their beverages after stress, compared to no stress. Stress increased anxiety, uneasiness, and produced some stimulant-like effects and, in the ethanol group, it dampened some of the acute subjective effects of ethanol. The direct physiologic and mood effects of the stress were fairly short-lived., Conclusions: It is concluded that acute stress may produce a modest increase in alcohol consumption in healthy, nonproblem social drinkers but that this increase is not directly related to the pharmacological effects of the drug. Nonpharmacological factors may include expectancies, thirst, or nonspecific facilitation of ongoing behaviors.